Investigation of the structural dynamics of a knotted protein and its unknotted analog using molecular dynamics

• Published in: Journal of molecular modeling 2022-04, Vol.28 (4), p.108-108, Article 108
• Main Authors: Silva, José Cícero Alves, Chaves, Elton José Ferreira, de Carvalho, Gabriel Aires Urquiza, Rocha, Gerd Bruno
• Format: Article
• Language: English
• Subjects: Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Cross correlation; Dynamic structural analysis; Knots; Molecular dynamics; Molecular Medicine; Original Paper; Principal components analysis; Proteins; Stability analysis; Theoretical and Computational Chemistry; Trajectory analysis
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-022-05094-y

The role of knots in proteins remains elusive. Some studies suggest an impact on stability; the difficulty in comparing systems to assess this effect, however, has been a significant challenge. In this study, we produced and analyzed molecular dynamic trajectories considering three different temperatures of two variants of ornithine transcarbamylase (OTC), only one of which has a 3 1 knot, in order to evaluate the relative stability of the two molecules. RMSD showed equilibrated structures for the produced trajectories, and RMSF showed subtle differences in flexibility. In the knot moiety, the knotted protein did not show a great deal of fluctuation at any temperature. For the unknotted protein, the residue GLY243 showed a high fluctuation in the corresponding moiety. The fraction of native contacts (Q) showed a similar profile at all temperatures, with the greatest decrease by 436 K. The investigation of conformational behavior with principal component analysis (PCA) and dynamic cross-correlation map (DCCM) showed that knotted protein is less likely to undergo changes in its conformation under the conditions employed compared to unknotted. PCA data showed that the unknotted protein had greater dispersion in its conformations, which suggests that it has a greater capacity for conformation transitions in response to thermal changes. DCCM graphs comparing the 310 K and 436 K temperatures showed that the knotted protein had less change in its correlation and anti-correlation movements, indicating stability compared to the unknotted. Graphical abstract